Using Mass Spectrometry for Biochemical Studies on Enzymatic Domains from Polyketide Synthases

This thesis reports studies on the
substrate specificity of crucial ketosynthase (KS) domains from trans-AT
Polyketide Synthases (PKSs). Using a combination of electrospray
ionisation-mass spectrometry (ESI-MS) and simple N-acetyl cysteamine (SNAC)
substrate mimics, Matthew Jenner has successfully studied the specificity of a
range of KS domains from the bacillaene and psymberin PKSs with regard to the
initial acylation step of KS-catalysis. The findings in this thesis provide
important insights into mechanisms of KS specificity and show that mutagenesis can
be used to expand the repertoire of acceptable substrates for future PKS
engineering. The documentation of this research is a useful reference and
guideline for students starting a PhD in this field.